Fructose Metabolism Contributes to the Warburg effect

Fructose metabolism is increasingly recognized as a preferred energy source for cancer cell proliferation. However, it remains unclear why cancer cells favor fructose metabolism and how they acquire a sufficient amount of fructose. Here we report that cancer cells convert glucose into fructose through intra- and extracellular polyol pathways. The fructose metabolism bypasses normal aerobic respiration’s self-control to supply excessive metabolites to glycolysis and promotes the Warburg effect. Inhibition of fructose production drastically suppressed glycolysis and ATP production in cancer. Furthermore, we determined that a glucose transporter, SLC2A8/GLUT8, exports intracellular fructose to other cells in the tumor microenvironment. Taken together, our study suggests that the Warburg effect is achieved by means of fructose metabolism, instead of glucose metabolism alone.